Imamichi Tomozumi, Yang Jun, Huang Da Wei, Sherman Brad, Lempicki Richard A
Laboratory of Human Retrovirology, Clinical Services Programs (CSP), Applied Developmental Directorate (ADD), Science Applications International Corporation (SAIC)-Frederick, Inc., National Cancer Institute (NCI)-Frederick, Frederick, MD 21702, USA.
Methods Mol Biol. 2012;820:25-53. doi: 10.1007/978-1-61779-439-1_3.
We have previously demonstrated that IL-27 is a novel anti-HIV cytokine, which inhibits HIV replication in CD4 T cells and macrophages as interferon (IFN)-α does. To further understand the mechanism of the antiviral effect, we performed Affymetrix DNA microarray and gene functional annotation analysis using DAVID (the Database for Annotation, Visualization, and Integrated Discovery). DAVID is a web-based bioinformatics application that systematically identifies enriched biology associated with large gene list(s) derived from high-throughput genomic experiments, such as microarray. The enriched annotation terms identified by DAVID will give important insights into understanding the biological themes under study. Having used the DAVID bioinformatics tools, we have shown that IL-27 differentially regulates the gene expression between T cells and macrophages. IL-27 significantly induces IFN-inducible genes including antiviral genes in macrophages as does IFN-α, suggesting that IL-27 inhibits HIV replication in macrophages via a mechanism similar to that of IFN-α.
我们之前已经证明，IL-27是一种新型抗HIV细胞因子，它像干扰素（IFN）-α一样抑制CD4 T细胞和巨噬细胞中的HIV复制。为了进一步了解抗病毒作用的机制，我们使用DAVID（注释、可视化和综合发现数据库）进行了Affymetrix DNA微阵列和基因功能注释分析。DAVID是一个基于网络的生物信息学应用程序，它系统地识别与来自高通量基因组实验（如微阵列）的大基因列表相关的富集生物学信息。DAVID识别出的富集注释术语将为理解所研究的生物学主题提供重要见解。使用DAVID生物信息学工具后，我们发现IL-27对T细胞和巨噬细胞之间的基因表达有不同的调节作用。IL-27与IFN-α一样，在巨噬细胞中显著诱导包括抗病毒基因在内的IFN诱导基因，这表明IL-27通过与IFN-α类似的机制抑制巨噬细胞中的HIV复制。
